This application is for continued support of a broad, ongoing program of research on the metabolism and enzymology of normal and neoplastic tissues. Specific areas of study are: 1. A study of isozyme patterns and enzyme regulation in a series of transplantable rat hepatomas in relation to growth rate and degree of differentiation. This is a continuation of previous work, which points to re-expression in poorly differentiated hepatomas, of isozymes which were expressed during the fetal stage, but suppressed during normal embryonic development. Current work is focused on the nature and properties of isozymes of pyruvate kinase, carbamyl phosphate synthetase, creatine kinase and phosphoenolpyruvate carboxykinase. 2. A combined immunochemical-radiochemical study of the rates of synthesis and degradation of phosphoenolpyruvate carboxykinase in a well differentiated hepatoma, the Reuber H-35, in cell culture and the influence thereon of insulin, cortisol, and cyclic AMP (with Dr. Richard Hanson). 3. A new research program on mechanisms and pathways of dechlorination of organohalides. Using the perfused rat liver, and various tissue preparations of rats and mice, we plan to study the release of chloride ion from model carcinogenic organochlorides, such as carbon Actrachloride and Chloroform.